This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Heterozygous deficiency of C1 esterase inhibitor (C1INH) leads to the clinical disease known as Hereditary Angioedema (HAE). This disease is characterized by attacks of non-itching swellings of the skin or mucosa. These swellings in general last for 2 to 3 days after which they resolve. Acute attacks of angioedema may be life-threatening if sites like the larynx are affected, and are often associated with significant morbidity during gastrointestinal attacks. Hence, HAE attacks require prompt treatment, often in an emergency room. Administration of C1INH-nf might also be warranted as prophylactic treatment. Administration of C1INH products purified from pooled plasma from normal donors has become routine clinical practice to treat attacks of HAE in countries where the therapy is available. Hypothesis: This is a superiority trial to demonstrate that subjects treated with prophylactic C1INH-nf have fewer attacks of angioedema compared to placebo. The null hypothesis for this study is that the difference in the total number of attacks of angioedema an HAE subject experiences during the period when he/she is receiving prophylactic C1INH-nf treatments compared to the period when he/she is receiving placebo treatments will be zero. The alternative hypothesis will be that the subject will experience a different number of angioedema attacks during the placebo treatment period compared to the C1INH-nf treatment period.